Researcher Enlists a Bug to Fight Resistant Organisms

PHILADELPHIA -- Fighting dangerous microbes has become increasingly difficult as many bacterial strains have become resistant to antibiotics. To respond to this problem, Laszlo Otvos, Jr., PhD, research professor and director of drug development at the Sbarro Institute of Cancer Research and Molecular Medicine at TempleUniversity in Philadelphia, has developed an antimicrobial peptide -- a fragment of a larger protein found in a certain insect -- that can identify resistant bacteria and target it for destruction. This March, Otvos was awarded a patent for his discovery, which he hopes will lead to a new class of peptide-based antibiotic drugs. Another patent application of the inventor, identifying an unprecedented mode of action of this particular class of novel antibiotics, is currently in the prosecution stage.

Along with the antimicrobial response of this peptide, Otvos' lab also identified the specific segments of the antimicrobial peptide that kill bacteria and the segments responsible for entering the cell to destroy it.

"Knowing how the peptides penetrate cells may be important for future drug delivery systems, against bacteria and deranged human cells alike," says Otvos.

Otvos, who earlier this year left the Wistar Institute where he was an associate professor in immunology, was also part of a research team who recently announced promising developments in a cancer vaccine for melanoma. Scientists working on the cancer vaccine employed a peptide that was designed by Otvos, found in about 70 percent of melanoma cells, to boost immune cells called killer T cells to identify and attack cancerous cells. Although a melanoma vaccine based on these discoveries has not yet been tested in humans, researchers estimate that the drug may eventually be effective in about a third of melanoma patients.

Otvos also designed and manufactured a prototype of a universal flu vaccine co-developed by his biologist partner, professor Walter Gerhard of Wistar. The vaccine, which passed the scrutiny of mouse testing and is currently in larger animal trials, would include protection against the avian flu, A (H5N1).

Present flu vaccines trigger the development of antibodies that target two specific proteins that sit on the influenza virus, hemagglutinin (HA) and neuraminidase (NA). The new vaccine sets its sights on M2, a much smaller protein that doesn't attract much of a response from the immune system.

"What makes M2 attractive is its stability," Otvos explains. "Unlike the other two proteins, it doesn't mutate as much. This means that a vaccine based on M2 doesn't need to be changed every time the virus evolves and that the vaccine protection will last much longer."

Otvos' contribution to the universal vaccine is a synthetically engineered peptide that will prompt the body to attack the relatively stable M2 protein. Several qualities make a synthetic peptide attractive: if it is eventually approved for use, the vaccine will be much easier to produce at higher levels of purity than egg-based vaccines. It also could be inhaled nasally, avoiding the pain of an injection.

Source: Sbarro Health Research Organization